ObjectivesEsophageal cancer (EC) is a significant global health concern. Human papillomavirus (HPV) has been proposed as a potential etiological factor, though its role, especially in esophageal adenocarcinoma (EAC), remains controversial. This study aims to systematically review and update the meta-analysis of HPV prevalence in both esophageal squamous cell carcinoma (ESCC) and EAC, and to assess the association between HPV infection and EC risk.MethodsA comprehensive literature search of PubMed, Scopus, and Web of Science was performed to identify studies published between January 1, 2000, and November 28, 2025 that reported HPV prevalence in EC, with a specific focus on both ESCC and EAC. Data on HPV genotypes, detection methods, and study characteristics were extracted and analyzed using random-effects models. Prevalence estimates were calculated for various detection methods, and meta-regression was used to identify sources of heterogeneity.ResultsA total of 151 studies, including 18,913 EC cases, were analyzed. HPV prevalence in EC varied by detection method, with polymerase chain reaction (PCR)-based studies showing an overall prevalence of 31% (95% CI: 25%−36%). Regionally, East Asia exhibited the highest prevalence (44%, 95% CI: 35%−53%). HPV prevalence was consistently higher in ESCC (29%, 95% CI: 23%−36%) compared to EAC (16%, 95% CI: 5%−30%). HPV-16 was the most prevalent genotype, showing a stronger association with ESCC than EAC. Meta-regression identified geographic region as a significant predictor of HPV prevalence. A pooled odds ratio (OR) of 2.92 (95% CI: 2.19–3.90) indicates a strong association between HPV infection and increased EC risk.ConclusionsHPV infection—particularly HPV-16—is epidemiologically associated with esophageal cancer, with higher detection rates observed in ESCC. However, current evidence is insufficient to establish HPV as a definitive causal driver of EC, especially for EAC, due to the predominance of observational designs and limited mechanistic confirmation.

Objectives:To assess the burden and trends of ischemic heart disease (IHD) and the risk-attributable fractions in women of childbearing age (WCBA) from 1990 to 2021 across 204 countries and territories. Methods:Data on the number and crude rates of incidence, mortality, disability-adjusted life years (DALYs), and the proportion attributable to risk factors were obtained from the Global Burden of Disease Study 2021. Temporal trends were assessed by calculating the estimated annual percentage change in age-standardized rate. Results:In 2021, there were 1,349,518 [95% uncertainty interval (UI), 924,620-1,849,024] new cases of IHD among WCBA, resulting in 172,204 (95% UI, 157,564-188,669) deaths and 8,712,835 (95% UI, 7,995,218-9,531,167) DALYs globally. From 1990 to 2021, the age-standardized incidence rate increased by a slight annual change of 0.4%, while the age-standardized mortality and DALY rates declined by 1.04% and 1.02% annually, respectively. Regional analysis revealed the highest IHD burden in North Africa and the Middle East, while Oceania reported the highest mortality-to-incidence ratio. While the age-standardized mortality and DALYs rates of IHD have shown a declining trend in low- and middle-SDI regions, the absolute numbers of deaths and DALYs have risen substantially. Attributable risks, including poor diet, tobacco use, high body mass index, and high blood pressure, were major contributors to IHD-related deaths and DALYs. Notably, the proportion of IHD attributable to high BMI and high blood pressure has increased, particularly in higher-SDI regions. Conclusions:The burden of IHD among WCBA is rising globally, with significant regional disparities and increasing attributable risks, particularly in low- and middle-SDI regions. These findings highlight the urgent need for targeted, gender-responsive policies and preventive strategies that address modifiable risk factors, strengthen primary healthcare systems, and prioritize cardiovascular health across the life course.

BackgroundRelatively little is known about long COVID (LC) in China, particularly regarding the effects of recent Omicron sub-lineages. Therefore, we systematically assessed the prevalence and risk factors for developing LC.MethodsThis retrospective cohort study included COVID-19 patients who had been hospitalized at two hospitals in Changzhi, China, between December 15, 2022 and April 30, 2024. All patients were interviewed via telephone ≥ 3 months after discharge. The follow-up study was conducted between July 18 and August 20, 2024. Logistic regression models were used to analyze risk factors for developing long COVID.ResultsA total of 2,765 patients (1,407 male [50.9%]; median [IQR] age 70.0 [59.0–78.0] years) were successfully evaluated by telephone; 458 (16.6%) self-reported long COVID symptoms. The most common symptom was fatigue (4.9%), followed by muscle weakness (3.9%), sleep difficulties (3.0%), brain fog (2.8%) and cough (2.5%). Severe COVID-19 patients had a higher risk of LC than non-severe patients (OR = 1.275, 95% CI: 1.036–1.570). In subgroup analyses stratified by follow-up time, overweight patients (OR = 1.564; 95% CI: 1.052–2.326), patients with ≥ 7 acute-phase symptoms (OR = 1.275; 95% CI: 1.064–1.528), and farmer (OR = 1.439, 95% CI: 1.047, 1.976) had a higher risk of LC, whereas individuals who received immunosuppressant therapy had a lower risk (OR = 0.691, 95% CI: 0.504, 0.948). In addition, aged ≥ 50 years (OR = 2.441, 95% CI: 1.175–5.072) and underweight status (OR = 2.183; 95% CI: 1.115–4.273) were associated with a higher risk of muscle weakness.ConclusionThis study provides valuable insights into LC after discharge, with 16.6% of discharged patients reporting symptoms. It is essential to monitor at-risk individuals according to identified risk factors for public health efforts.

BackgroundUnderstanding the persistence of long COVID (LC) among discharged patients with Omicron infection remains limited.MethodsThe study used a retrospective longitudinal cohort to evaluate the dynamic trajectory of LC after hospital discharge and to identify factors associated with new-onset and persistent LC following Omicron infection. Patients admitted to Heping Hospital Affiliated to Changzhi Medical College and Changzhi People’s Hospital for coronavirus disease 2019 between 15 December 2022 and 30 April 2024 were included. The first follow-up was conducted from 18 July to 20 August 2024, and the second from 9 May 2025 to 13 June 2025.ResultsOf the 3,777 discharged patients, 1,922 [median (IQR) age, 70.0 (59.0–78.0) years; 968 male individuals (50.4%)] who completed both follow-up visits were included in the final analysis. The median (IQR) time from discharge to the second follow-up was 727 (688–854) days. At the second follow-up, 292 patients (15.2%) were diagnosed with LC, including 121 (6.3%) with persistent LC and 171 (8.9%) with new-onset LC. The most common symptoms were muscle weakness, sleep difficulties, fatigue, cough, and dyspnea at rest. Notably, the proportions of muscle weakness, sleep difficulties, cough, arthralgia, and palpitations increased significantly, whereas brain fog decreased significantly from 2.8% at the first follow-up to 0.4% at the second follow-up. Overall, antiviral treatment (OR = 1.503; 95% CI: 1.063–2.126), female sex (OR = 3.729; 95% CI: 1.145–12.147), being a farmer as an occupation (OR = 4.695; 95% CI: 2.188–10.101), and BMI < 18.5 kg/m2 (OR = 5.291; 95% CI: 1.115–25.000) were associated with increased new-onset LC susceptibility, whereas having one or more complications was associated with decreased new-onset LC susceptibility (OR = 0.329; 95% CI: 0.125–0.865).ConclusionOmicron-infected patients report a persistent burden of symptoms consistent with the WHO definition of LC after discharge. These findings provide valuable information on the dynamic trajectory of long-term health outcomes in patients infected with Omicron. However, the non-specific nature of the symptoms should be considered when interpreting these findings.

BackgroundThe association of the p53 rs1042522 and rs17878362 polymorphisms with cervical cancer risk has been reported in several published original studies and meta-analyses. However, the conclusions of these studies were contradictory. Consequently, we conducted an updated meta-analysis to further validate these debates.ObjectiveTo evaluate the association between the p53 rs1042522 and rs17878362 polymorphisms and cervical cancer risk.Materials and MethodsPubMed, Medline, Ovid, Embase, CNKI, and China Wanfang databases were searched. Association was assessed using odds ratio (OR) with 95% confidence interval (CI). Moreover, the false-positive reporting probability (FPRP), Bayesian false-finding probability (BFDP), and Venice criteria were used to assess the credibility of statistically significant association.ResultsA significantly decreased cervical cancer risk was revealed for the p53 rs1042522 polymorphism (Pro/Pro +Arg/Pro vs. Arg/Arg: OR = 0.79, 95% CI = 0.71-0.87; Pro/Pro vs. Arg/Arg: OR = 0.80, 95% CI = 0.70-0.91; Arg/Pro vs. Arg/Arg: OR = 0.78, 95% CI = 0.71-0.86; Pro vs. Arg: OR = 0.87, 95% CI = 0.81-0.93) in overall analysis and several subgroup analyses, such as in Caucasians, Asians, Indians, and so on. However, no significant association was found between the p53 rs17878362 polymorphism and cervical cancer risk. Despite these statistically significant results, reliability analysis using FPRP, BFDP, and Venice criteria deemed all associations “unreliable”.ConclusionsAfter considering the reliability of the results, this study indicates that the p53 rs1042522 polymorphism is not associated with the cervical cancer risk.

PurposeThe global prevalence and trends of gynecological diseases (GDs) among women of childbearing age (WCBA) remain unclear and may be underestimated. This study aims to evaluate the prevalence of GDs at global, regional, and national levels and assess changes from 1990 to 2021.MethodsData on the annual prevalence of major GDs, including uterine fibroids, polycystic ovarian syndrome (PCOS), female infertility, endometriosis, genital prolapse, premenstrual syndrome (PMS), and other GDs, were obtained from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The study analyzed women aged 15-49 years across 204 countries and territories from 1990 to 2021. Estimated annual percentage changes (EAPC) in the age-standardized prevalence rate (ASPR) were calculated to quantify temporal trends, by age and socio-demographic index (SDI).ResultsIn 2021, the global prevalence of GDs among WCBA was estimated at 1.21 billion cases, corresponding to a ASPR of 62,091.73 cases per 100,000 population (95% UI: 62,088.24 to 62,095.23). While the ASPR for GDs remained stable from 1990 to 2021 (EAPC = 0% [95% CI: -0.03 to 0.02]), the number of prevalent cases doubled over the same period. In 2021, the most prevalent GD globally was PMS, followed by uterine fibroids, PCOS, and female infertility. Conditions such as uterine fibroids, PCOS, and female infertility showed a significant upward trend in ASPR over time. Additionally, the ASPR of most GDs generally decreased with rising SDI, except for PCOS, which exhibited an increasing trend with higher SDI. The prevalence of GDs also increased with age, peaking in the 40-44 years age group. However, a shift in the burden of GDs toward younger women was observed, with significant increases in prevalence rates for uterine fibroids, PCOS, female infertility, and PMS in women aged 20-29 years.ConclusionsGDs among WCBA remain a global concern, underscoring the urgent need for targeted interventions, especially for younger populations and in regions with limited healthcare infrastructure. Prioritizing early intervention, addressing environmental risk factors, and removing barriers to healthcare access will mitigate the long-term impact of these conditions on women's health and overall well-being.

BACKGROUND:Bladder cancer (BLCA) represents one of the most prevalent malignant neoplasms within the urinary system, and its incidence is progressively rising annually in China. OBJECTIVES:This research investigated the clinical significance of DLGAP1-AS2, and examined its potential mechanisms in modulating the behavior of BLCA cells. METHODS:This study collected cancerous and normal tissue samples from 86 BLCA patients. qPCR was employed to assess DLGAP1-AS2 and miR-451a expression. Chi-square test was utilized to analyze the correlation between DLGAP1-AS2 and clinical parameters. Cox model and Kaplan-Meier analysis were conducted to evaluate the association between DLGAP1-AS2 and the prognosis of BLCA patients. Furthermore, DLGAP1-AS2 was silenced, both independently and jointly with miR-451a, in BLCA cell lines. CCK-8 assay assessed cell proliferation, and the Transwell assay evaluated cell migration and invasion capabilities. RESULTS:DLGAP1-AS2 was elevated in BLCA tissues and exhibited a correlation with both smoking history and pathological features in BLCA patients. DLGAP1-AS2 was identified as a prognostic risk factor, wherein patients exhibiting low expression had a more favorable prognosis. DLGAP1-AS2 was up-regulated in BLCA cells, and its silencing led to a reduction in the proliferation, migration, and invasion of BLCA cells. Conversely, miR-451a was down-regulated in BLCA tissues and cells, and it demonstrated a negative regulatory interaction with DLGAP1-AS2. The concurrent silencing of DLGAP1-AS2 and miR-451a effectively restored the biological behaviors of BLCA cells. CONCLUSION:DLGAP1-AS2 is a potential biomarker for evaluating the severity of BLCA and for predicting clinical prognosis. DLGAP1-AS2 regulates the malignant progression of BLCA via miR-451a.

Objectives:Stroke is increasingly affecting young adults, with metabolic-risk factors playing a critical role in this trend. This study aims to assess the global burden and trends of stroke and its subtypes attributable to metabolic-risks in young adults from 1990 to 2021. Methods:Data from the Global Burden of Disease Study (GBD) 2021 were analyzed to assess the disability-adjusted life years (DALYs) attributed to metabolic-risks for stroke and its subtypes in young adults across 204 countries and territories. Estimated annual percentage changes in the age-standardized DALYs rate (ASDR) of stroke, by age, sex, socio-demographic index (SDI), and subtype, were calculated to quantify the temporal trends. Results:In 2021, metabolic risk factors were responsible for approximately 3,960,349 stroke-DALYs in young adults globally, accounting for 45.44% of the total stroke burden in this group. High systolic blood pressure was the leading contributor (35.43%), followed by high LDL cholesterol (9.13%), high BMI (7.26%), kidney dysfunction (5.47%), and high fasting plasma glucose (2.42%). From 1990 to 2021, the absolute number of stroke-related DALYs attributable to metabolic-risks increased by 22.23%, while the ASDR decreased by 0.78% annually. Regional disparities were evident, with East Asia reporting the largest number of stroke-DALYs attributable to metabolic-risks and Southeast Asia exhibiting the highest ASDR. Notably, the proportion of stroke-DALYs attributable to metabolic-risks showed a positive association with SDI and increased across all regions during the study period. The most notable increases were observed in Eastern Europe. By stroke subtype, metabolic risk factors contributed to 1,147,521 DALYs from ischemic stroke, 2,267,874 from intracerebral hemorrhage, and 544,954 from subarachnoid hemorrhage in 2021. The ASDR of all subtypes declined from 1990 to 2021, with the steepest decline for subarachnoid hemorrhage (EAPC = -1.37%). However, ASDR increased in specific regions, notably Sub-Saharan Africa for ischemic stroke and the Caribbean and Oceania for intracerebral hemorrhage and subarachnoid hemorrhage. Conclusions:Despite a decline in ASDR, the absolute burden of stroke attributable to metabolic risks among young adults has increased globally, with significant regional and national disparities. Targeted prevention strategies addressing metabolic risk factors are urgently needed, particularly in high-burden regions.

BACKGROUND:The impact of surgical compliance on survival outcomes in patients with Ewing sarcoma (ES) is unclear, so this study was performed to explore the association between them. METHODS:We used the SEER*Stat software (version 8.3.6.1) to extract information on ES patients from the SEER database. Patients were divided into two groups based on their adherence to surgical recommendations: the surgical compliance group and the surgical noncompliance group. Categorical variables were expressed as percentages. Multivariate logistic regression and Chi-square test were used to explore variables related to surgical compliance. Univariate Cox regression analysis was used to initially select potential prognostic factors, and then the factors selected in the univariate Cox regression analysis were further analyzed in a multivariate Cox proportional risk model to ultimately determine the risk prognostic factors significantly related to the survival of patients with ES. RESULTS:Multiple logistic regression analysis suggested that adults (OR = 0.373, 95% confidence interval (CI): 0.164-0.849), Grade IV (OR = 0.373, 95% CI: 0.164-0.849), and unmarried patients (OR = 0.568, 95% CI: 0.339-0.954) were more inclined to accept surgery recommendations, while patients from 2001 to 2010 were less compliant with surgery. Multifactorial Cox regression analysis suggested that surgical compliance was an independent prognostic factor for patients with ES. Through the Kaplan-Meier survival curves, we could clearly observe that the overall survival was higher in the surgical compliance group than in the surgical noncompliance group. Furthermore, subgroup analysis also reached similar conclusions. CONCLUSION:In this study, we found that surgical compliance was an independent predictor of patient prognosis. Furthermore, we found that age, tumor grade, year of diagnosis, and marital status may be related to surgical compliance.

Type 1 diabetes (T1D) is a significant global health concern, characterized by the autoimmune destruction of insulin-producing pancreatic β-cells, resulting in lifelong dependence on insulin therapy. Although genetic predisposition plays a crucial role in the pathogenesis of T1D, environmental factors also contribute to its onset and progression. Recent research has identified a number of genetic polymorphisms, particularly in the protein tyrosine phosphatase non-receptor 22 gene (PTPN22), that are strongly associated with an increased risk of T1D and may serve as potential biomarkers for early diagnosis and prevention. Despite this, studies investigating the relationship between PTPN22 rs2476601 and T1D risk have consistently demonstrated an association in certain populations, whereas research on rs1310182 has yielded conflicting and less conclusive results. This study presents an updated meta-analysis of two key PTPN22 polymorphic loci - rs2476601 (C1858T) and rs1310182 (A852G) - with the aim of clarifying their associations with T1D. The analysis revealed a significant association between PTPN22 rs2476601 and an increased risk of T1D. In contrast, no significant correlation was found for rs1310182. These findings suggest that PTPN22 rs2476601 as a marker for T1D susceptibility, offering insights into the development of early intervention strategies. However, further research is required to validate these associations and deepen our understanding of the genetic factors involved in T1D pathogenesis.

[This corrects the article DOI: 10.3389/fgene.2022.959291.].

Colorectal cancer pathogenesis is a multifactorial process, with genetic factors playing a significant role in cancer development. A review of published meta-analyses on MTHFR gene polymorphisms and colorectal cancer susceptibility showed inconsistent findings and failed to assess the reliability of statistically significant results. Case-control studies were manually searched in databases to investigate the association between MTHFR gene polymorphisms and colorectal cancer. The study assessed the strength of association for the five gene models by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The study results were also analyzed for the source of heterogeneity, sensitivity, publication bias, and false-positive report probability (FPRP) test. Additionally, extensive subgroup analyses were conducted to investigate the impact of confounding factors on the associations. The study suggests that MTHFR C677T gene polymorphism reduces the risk of colorectal cancer in Asian and mixed-race populations, while increasing the risk of Colorectal cancer in the Indian ethnic group. MTHFR A1298C may play a protective role in the development of colorectal cancer. These findings provide valuable insights for the early diagnosis and prevention of Colorectal cancer. However, further studies are required to confirm the association, which may offer additional information for the early diagnosis and prevention of Colorectal cancer.

ObjectivesOur aim was to explore the disease burden caused by gallbladder and biliary tract cancer globally, regionally, and nationally, by age and sex.MethodsThe absolute number of cases and age-standardized rates (ASR) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) due to gallbladder and biliary tract cancer were extracted from the Global Burden of Disease (GBD) Study 2019. We estimated the trends in disease burden by calculating the percentage change in the absolute number of cases and the estimated annual percentage change (EAPC) in ASR, by social development index (SDI), region, nation, sex, and age.ResultsFrom 1990 to 2019, the number of incident cases, prevalent cases, deaths, and DALYs worldwide significantly increased by 1.85-fold, 1.92-fold, 1.82-fold, and 1.68-fold, respectively. However, the age-standardized rates of incidence, prevalence, mortality, and DALYs tend to decrease globally over time. Nevertheless, heterogeneous disease burden patterns exist between geographic regions due to different geographical risk factors, distinct epidemiologically predominant gallbladder and biliary tract cancer subtypes, and potential genetic predispositions or ethnicity. Additionally, socioeconomic status mediates the regional variation in disease burden, with increasing SDI or HDI scores associated with downward trends in the age-standardized rates of incidence, prevalence, mortality, and DALYs. Older individuals and females are at higher risk of gallbladder and biliary tract cancer, but the increasing burden of early-onset gallbladder and biliary tract cancer is a cause for concern, especially for those living in lower SDI areas and males. High BMI is the primary risk factors underlying gallbladder and biliary tract cancer, accounted for 15.2% of deaths and 15.7% DALYs globally in 2019.ConclusionOur study comprehensively elucidated the distribution and dynamic trends of gallbladder and biliary tract cancer burden over the past three decades, from multiple dimensions. These findings emphasize the importance of promoting a healthy lifestyle as a population-level cancer prevention strategy and tailoring cancer control actions based on localized risk factors and the epidemic profiles of gallbladder and biliary tract cancer by anatomical subtype.

Purpose While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin. Materials and Methods This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30–50), 75 (range, 60–90), or 100 (range, 75–125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. Results Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere ( n = 9), epirubicin ( n = 9), or procedure ( n = 12) with none resulting in death. Conclusion DEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. Level of evidence 2, Prospective, Non-randomized, Single-arm, study. Graphical Abstract

Little studies evaluated the effectiveness of booster vaccination of inactivated COVID-19 vaccines against being infected (susceptibility), infecting others (infectiousness), and spreading the disease from one to another (transmission). Therefore, we conducted a retrospective cohort study to evaluate the effectiveness of booster vaccination of inactivated COVID-19 vaccines against susceptibility, infectiousness, and transmission in Shenzhen during an Omicron BA.2 outbreak period from 1 February to 21 April 2022. The eligible individuals were classified as four sub-cohorts according to the inactivated COVID-19 vaccination status of both the close contacts and their index cases: group 2-2, fully vaccinated close contacts seeded by fully vaccinated index cases (reference group); group 2-3, booster-vaccinated close contacts seeded by fully vaccinated index cases; group 3-2, fully vaccinated close contacts seeded by booster-vaccinated index cases; and group 3-3, booster-vaccinated close contacts seeded by booster-vaccinated index cases. Univariate and multivariate logistic regression analyses were applied to estimate the effectiveness of booster vaccination. The sample sizes of groups 2-2, 2-3, 3-2, and 3-3 were 846, 1,115, 1,210, and 2,417, respectively. We found that booster vaccination had an effectiveness against infectiousness of 44.9% (95% CI: 19.7%, 62.2%) for the adults ≥ 18 years, 62.2% (95% CI: 32.0%, 78.9%) for the female close contacts, and 60.8% (95% CI: 38.5%, 75.1%) for the non-household close contacts. Moreover, booster vaccination had an effectiveness against transmission of 29.0% (95% CI: 3.2%, 47.9%) for the adults ≥ 18 years, 38.9% (95% CI: 3.3%, 61.3%) for the female close contacts, and 45.8% (95% CI: 22.1%, 62.3%) for the non-household close contacts. However, booster vaccination against susceptibility did not provide any protective effect. In summary, this study confirm that booster vaccination of the inactivated COVID-19 vaccines provides low level of protection and moderate level of protection against Omicron BA.2 transmission and infectiousness, respectively. However, booster vaccination does not provide any protection against Omicron BA.2 susceptibility.

BackgroundRising trends in early-onset colorectal cancer (CRC) burden have been observed, but the distribution and temporal patterns of early-onset CRC attributable to dietary risks remain unclear.ObjectivesThis study aimed to estimate the burden of early-onset CRC attributable to dietary risk factors globally, regionally, and nationally, by age and sex, from 1990 to 2019.MethodsThe absolute number and age-specific rates (ASR) of diet-related early-onset CRC burden, as well as summary exposure value (SEV) of attributable dietary risk factors, were extracted from the Global Burden of Disease (GBD) Study 2019. The temporal changes in the burden between 1990 and 2019 were analyzed by calculating the percentage change in the absolute number of burden and the estimated annual percentage change (EAPC) in ASR of burden. The annualized rates of change (ARC) were calculated to evaluate the variation trend of SEV.ResultsIn 2019, diet-related early-onset CRC caused 30,096 (95% UI: 23,148 to 36,091) death cases and 1,465,755 (95% UI: 1,126,489 to 1,761,661) DALYs worldwide, accounting for 34.8% deaths and 34.4% DALYs of overall early-onset CRC, respectively. Moreover, a diet low in milk (responsible for 16.5% [95% UI: 11.1 to 21.9%] of DALYs in 2019), low in whole grains (15.2% [95% UI: 5.9 to 19.9%]), low in calcium (14.3% [95% UI: 10.7 to 18.9%]), high in red meat (5.3% [95% UI: 1.7 to 9.5%]), high in processed meat (2.5% [95% UI: 0.9 to 4.0%]), and low in fiber (2.3% [95% UI: 0.9 to 4.2%]) were early-onset CRC attributable dietary risk factors. The age-specific DALYs rate of early-onset CRC attributable to each dietary risk factor generally showed an increasing trend globally between 1990 and 2019, except for low intake of fiber (EAPC = −0.57, 95% CI: −0.76 to −0.38). In addition, from 1990 to 2019, males have a higher burden than females and this gap may continue to widen due to the increasing difference between the sexes in most dietary risk factors. Furthermore, dietary risks-attributable early-onset CRC burden has shifted from regions with high socio-demographic index (SDI) to high-middle and middle SDI quintiles with uncontrolled dietary risks.ConclusionEarly-onset CRC remains a concerning issue globally, and effective prevention and modification of dietary risk factors holds great promise to reduce early-onset CRC-related burden. Prioritizing diet improvement for males is critical and urgent for CRC control efforts, particularly for those living in developing countries with ongoing dietary pattern transition.

Purpose: To comprehensively assess the prevalence and risk factors of chemotherapy-induced oral mucositis in 470 children diagnosed with acute lymphoblastic leukemia in China, and to gain a better understanding of the treatment-related risk factors. Methods: In this retrospective study, 470 children diagnosed with acute lymphoblastic leukemia in China between January 2020 and July 2022 were included. Data on sociodemographic characteristics, nutritional status, disease and treatment history, blood biochemistry, and microbiological factors were gathered using electronic medical records, alongside oral and dietary information collected through field investigations and telephone follow-ups. The association between chemotherapy-induced oral mucositis and these variables was assessed using univariate and multivariate logistic analyses. Results: The study found a high prevalence (45.1%) of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia. The occurrence of oral mucositis was associated with several factors, including receiving more than five chemotherapy cycles (P<0.001), carrying HSV-1(P=0.016), being infected with Candida albicans(P=0.012), undergoing chemotherapy with specific drugs containing methotrexate/daunorubicin/cytarabine(P<0.001), having a high clinical risk stratification(P=0.002), and being over 6 years old(P=0.002). Conclusion: The study suggests that the prevalence of chemotherapy-induced oral mucositis in children with acute lymphoblastic leukemia is relatively high. It emphasizes the importance of clinical medical staff paying attention to this issue and adopting targeted interventions to reduce the prevalence of oral mucositis in this patient population.

OBJECTIVE:To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T (UBE2T) on radiosensitivity of hepatocellular carcinoma (HCC). METHODS:Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector, and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay. The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice, and tumor growth following irradiation were recorded. The xenografts were collected for analyzing infiltration of CD4+ T cells and regulatory T cells (Tregs) using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting. The correlations of UBE2T expression with immune cell infiltration, glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database, and the results were verified in a co-culture system of Hepa1-6 cells and Tregs. RESULTS:UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models (especially in C57BL/6 mice). CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells, T follicular helper cells, M2 macrophages, monocytes, lymphocytes and Tregs in HCC. The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA, and irradiation increased infiltration of CD4+ T cells and Tregs in the tumor microenvironment. Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration. GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC. In the cell co-culture system, UBE2T overexpression significantly enhanced lactate production, proliferation and immunosuppressive functions of Tregs. CONCLUSION:A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.

BackgroundThe global prevalence of aging individuals with multiple sclerosis (MS) is increasing. This study aimed to assess the burden and trends of overall and smoking-attributable MS in older adults aged 65–89 years at the global, regional, and national levels.MethodsThe number and rates of years of life lived with disability (YLD) and years of life lost (YLL) due to MS for older adults in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease (GBD) Study 2019. Estimated annual percentage change (EAPC) in the age-standardized YLD and YLL rates were calculated to quantify the temporal trends. The Bayesian age-period-cohort model was used to predict the trends from 2020 to 2040.ResultsIn 2019, there were an estimated 80,040 (95% uncertainty interval 57,534 to 103,608) YLD and 139,132 (107,632 to 161,172) YLL caused by MS among older adults globally. The age-standardized YLD and YLL rates decreased by an average of −0.21% (95% CI –0.26 to −0.16) and − 0.2% (95% CI –0.26 to −0.14) per year for overall MS from 1990 to 2019, respectively. The number of YLL globally in 2019 was 7,891 (5,003 to 10,991) and 15,667 (10,833 to 20,076) due to smoking-attributable MS. The age-standardized YLD and YLL rates decreased by an annual average of −1.14% (95% CI –1.25 to −1.04) and − 1.15% (95% CI –1.27 to −1.03) for MS attributable to smoking. Although the global age-standardized rates of YLD and YLL for MS among older adults declined from 1990 to 2019, many regions showed increases. The largest increase in age-standardized YLD rate of MS was observed in East Asia (average annual change 1.62% [95% CI: 1.56 to 1.68]), while the largest increase in the age-standardized YLL rate occurred in High-income North America (1.74% [1.53 to 1.96]). Nationally, the age-standardized YLD and YLL rates for overall and smoking-attributable MS increased exponentially with increases in SDI level (all model p < 0.001). Furthermore, projections have also indicated an expected decrease in the age-standardized rates of YLD and YLL of MS in the elderly population from 2020 to 2040.ConclusionTracking trends in MS burden among older adults provides insights into the potential shifts in disease patterns over time. The findings lay the groundwork for informed decision-making in public health and healthcare delivery, aiming to ensure that older adults with MS receive appropriate care and support.

We conducted a retrospective cohort study to evaluate the transmission risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 variant and the effectiveness of inactivated COVID-19 vaccine boosters in Shenzhen during a BA.2 outbreak period from 1 February to 21 April 2022. A total of 1,248 individuals were infected with the BA.2 variant, and 7,855 close contacts were carefully investigated. The risk factors for the high secondary attack rate of SARS-CoV-2 infection were household contacts [adjusted odds ratio (aOR): 1.748; 95% confidence interval (CI): 1.448, 2.110], younger individuals aged 0–17 years (aOR: 2.730; 95% CI: 2.118, 3.518), older persons aged ≥60 years (aOR: 1.342; 95% CI: 1.135, 1.588), women (aOR: 1.442; 95% CI: 1.210, 1.718), and the subjects exposed to the post-onset index cases (aOR: 8.546; 95% CI: 6.610, 11.050), respectively. Compared with the unvaccinated and partially vaccinated individuals, a relatively low risk of secondary attack was found for the individuals who received booster vaccination (aOR: 0.871; 95% CI: 0.761, 0.997). Moreover, a high transmission risk was found for the index cases aged ≥60 years (aOR: 1.359; 95% CI: 1.132, 1.632), whereas a relatively low transmission risk was observed for the index cases who received full vaccination (aOR: 0.642; 95% CI: 0.490, 0.841) and booster vaccination (aOR: 0.676; 95% CI: 0.594, 0.770). Compared with full vaccination, booster vaccination of inactivated COVID-19 vaccine showed an effectiveness of 24.0% (95% CI: 7.0%, 37.9%) against BA.2 transmission for the adults ≥18 years and 93.7% (95% CI: 72.4%, 98.6%) for the adults ≥60 years, whereas the effectiveness was 51.0% (95% CI: 21.9%, 69.3%) for the individuals of 14 days to 179 days after booster vaccination and 51.2% (95% CI: 37.5%, 61.9%) for the non-household contacts. The estimated mean values of the generation interval, serial interval, incubation period, latent period, and viral shedding period were 2.7 days, 3.2 days, 2.4 days, 2.1 days, and 17.9 days, respectively. In summary, our results confirmed that the main transmission route of Omicron BA.2 subvariant was household contact, and booster vaccination of the inactivated vaccines was relatively effective against BA.2 subvariant transmission in older people.